Menstrual Cycle II Flashcards
How does the switch to positive feedback occur? LH vs hCG (3)
1) LH surge lasts for 36-48 hours(>300pmmol threshold for 2 days)
2) triggers ovulation (timing varies from species-species)
» LH surge relatively precise predictor of timing of ovulation
3) LH is rapidly cleared from serum, in contrast to hCG (from blastocyst) which is cleared slowly & binds with great affinity to LHCGR
Where are LHr found on the follicle during follicle selection?
Theca + Granulosa cells - dominant follicle
Preovulatory Follicle changes after LH Surge and why (6)
prior:
-The eggs move into the middle- oocytes surrounded by cumulus cells (COC)
after:
-eggs move to the surface of ovary (ready for ovulation)
-loss of ovarian surface epithelium
-breakdown of underlying basal lamina, GranulosaC + ThecaC at apex (to allow rupture)
-GC basal lamina dirsrupted to allow extension of blood vessels into GC Layer + for infiltration of theca cells + leukocytes into GC compartment
-COC detaches from surrounding GC to expand
What factors are responsible for holding the oocyte in
meiotic arrest? (4)
‒ High cAMP → keep maturation promoting factor (MPF) inactive
‒ cGMP enters oocytes from cumulus cells via gap junctions to inhibit oocyte cAMP phosphodiesterase PDE3A activity (PDE3A normally degrades cAMP)
‒ H2O2/NO/calcium
‒ other cells/ ovarian environment & integrity of the follicle?
Effect of LH (7)
Within 3-12h of LH surge:
» Detachment of COC from surrounding mural GC, followed by cumulus cell expansion – formation of unique extracellular matrix between cumulus cells (aka “mucification”)
– Comprised of long chains of hyaluronan
– Visco-elastic properties of CC matrix important for successful ovulation, ovum pick up by oviducts and penetration of sperm
» ↓cGMP production and closure of gap junctions
» Activation of PDE3A → ↓cAMP → activation of pathways leading to breakdown of nuclear membrane in primary oocyte aka germinal vesicle breakdown (GVBD)
» Resumption of meiosis in oocyte → completion of Meiosis I & release of 1st polar body (23 chromosomes + a bit of cytoplasm)
» Arrests again in Metaphase II
LH surge and resumption of meiosis (10)
image
pre:
-high cGMP
- high cAMP
- preventing MAF from being active
post surge:
-close channels
-decrease cGMP
-activate PD3EA
-degraded cAMP
-GC breakdown
-meosis 1 starts
-maturation process start +finish
Meiosis in the Oocyte (6)
-Early oocytes classified as immature i.e. at germinal vesicle (GV) or metaphase 1 stage
-Meiosis I is completed with half chromosomes but nearly all cytoplasm remaining in the secondary oocyte
- Remaining chromosomes move with small bag of cytoplasm to form discarded polar body (PB)
-Chromosomes of secondary oocyte immediately enter 2nd
meiotic division, form the 2nd metaphase spindle and arrest
-This arrest is maintained by cytostatic factor (protein complex)
-Egg is ovulated in this arrested state
Why is there an unequal division of cytoplasm? (women>men)
All organelles, mitochondria (maternal mitochondria) - all energy needed for the early stages of pre-implantation for embryo development will come from the mature oocyte
LH surge & Ovulation - stigma creation (5)
-LH surge induces expression of progesterone receptor (PR) in GC = luteinisation of DF cells (both granulosa and theca)
-E2 production falls and P is stim. (because granulosa and theca luteal produce p)
-Blood flow to the follicle increases & new vessels appear in avascular GC
-Prostaglandins and proteolytic enzymes (e.g. collagenase and
plasmin) increased in response to LH and progesterone to digest collagen in follicle wall
-appearance of apex or stigma on ovary wall
» Stigma= point of the dominant follicle closest to the ovarian surface where digestion occurs
When does ovulation occur?
~12-18 hours (after the peak of LH surge)
Ovulation-post cascade of events (5)
Cascade of events → release of COC → Ovulation
1)Increased secretion of chemokine/cytokines from GC & TC triggers massive infiltration of leukocytes from circulation →
acute inflammatory response
2 )In humans – ovulation occurs randomly from either ovary during a given cycles, some indication more common from right ovary
(Progesterone essential for ovulation
» Progesterone inhibitor (RU486) suppress ovulation)
3)Prostaglandins-E and -F and hydroxyeicosatetraenoic acid (HETE metabolite of arachidonic acid) reach a peak level in follicular fluid just prior to ovulation
4) Prostaglandins stimulate proteolytic enzymes (proteases)
5) HETEs may stimulate angiogenesis and hyperemia (↑blood flow)
Follicle Rupture/Ovulation (2)
No increase in intra-follicular pressure
Progressive weakening of stigma region and OSE overlying follicle prior to rupture – fundamental aspect
What is involved in the rupture of the ovarian wall? (3)
1) LH stimulates secretion of Plasminogen Activator (PA)
2) Collagenase disrupts fibril network of theca & tunica albuginea & promotes digestion of basement membrane of follicle and OSE
3) TNF-alpha induces cell death, proteolysis, stigma formation and eventual follicular rupture
Ovulation pt2 (6)
Secondary oocyte (arrested in metaphase II) with cumulus cells is extruded from the ovary
follicular fluid may pour into Pouch of Douglas
egg ‘collected’ by fimbria of uterine tube
egg progresses down tube by peristalsis and action of cilia
Ciliated cells are controlled by which hormones?
Residual part of follicle collapses into space left by fluid – a clot forms and whole structure become corpus luteum
Inflammation Associated with Ovulation - effects (4)
The follicular fluid is “inflammatory”
Inflammation definitely present, but too much is detrimental…
Higher “inflammation markers” in FF associated with decreased pregnancy rate (specifically C Reactive Protein, CRP)
Gingivitis associated with poorer IVF outcomes!
